A Sequential Trial of Low-Dose Radiotherapy Followed by Concurrent Immunotherapy, Systemic Chemotherapy, and Intraperitoneal Perfusion in Gastric Cancer With Peritoneal Carcinomatosis

A Sequential Trial of Low-Dose Radiotherapy Followed by Concurrent Immunotherapy, Systemic Chemotherapy, and Intraperitoneal Perfusion in Gastric Cancer With Peritoneal Carcinomatosis

This study is a prospective, single-center, open-label, exploratory phase II clinical trial aimed at evaluating the safety, tolerability, and preliminary efficacy of low-dose radiotherapy (LDR) sequentially combined with serplulimab, bevacizumab analog, and irinotecan or albumin-bound paclitaxel in patients with gastric cancer and peritoneal metastases. A total of 40 patients with gastric adenocarcinoma who have previously undergone first-line therapy are planned for enrollment. Patients will be grouped based on prior exposure to paclitaxel-based chemotherapy to determine whether they will receive systemic treatment with irinotecan combined with serplulimab or albumin-bound paclitaxel combined with serplulimab, along with local intraperitoneal infusion of bevacizumab analog. The study adopts a Simon two-stage design, with 20 patients enrolled in the first stage. If ≥3 patients achieve objective remission, the study will proceed to the second stage, enrolling an additional 20 patients.

Inclusion Criteria:

• 1. Age >18 years on the day of signing the Informed Consent Form; 2. The subject is able to comprehend the procedures and methods of this clinical study, and voluntarily signs the informed consent form after providing full informed consent.

  3. Gastric or gastroesophageal junction adenocarcinoma (HER2-negative) confirmed by histology or cytology.

  4. Imaging confirmed metastases to peritoneum (PCI score ≥10), not suitable for radical excision 5. Failure of first-line platinum-based chemotherapy (due to progression or inability to tolerate).

  6. CT imaging or PET CT suggests metastases to the peritoneum, or ascites cytology is positive.

  7. ECOG PS 0-2, expected survival ≥3 months. 8. Organ function meets the following criteria (within 10 days of first receiving the investigational medicinal product).

  1. Hematology: Platelet count ≥100×10⁹/L, hemoglobin ≥8g/dL, ANC ≥1.5×10⁹/L, and no blood products, erythropoiesis-stimulating agents, or colony-stimulating factors therapy received within the past 7 days;

  2. Renal function: Serum creatinine is within the normal upper limit range set by the institution;

  3. Liver function: Total bilirubin ≤ 1.5×UNL; if total bilirubin > 1.5×UNL, then direct bilirubin should be ≤ UNL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both ≤ 2.5×UNL, albumin > 2.5 mg/dL;

  4. Coagulation function: International normalized ratio (INR), prothrombin time (PT), activated partial thromboplastin time (APTT) ≤1.5×UNL; if the subject is undergoing anticoagulation therapy, it should be within the established therapeutic range; 9. Women of childbearing age must have a negative serum pregnancy test within 72 hours prior to the first administration of the investigational medicinal product. If the urine test result is positive or cannot be confirmed as negative, further serum pregnancy testing is required.

     10. Women of childbearing age must agree to use two effective methods of birth control or undergo surgical sterilization, or choose to avoid any heterosexual intercourse throughout the study period and for 120 days after the last drug administration. (Women who have been postmenopausal for more than one year and have not undergone surgical sterilization are considered infertile.) Lactating women must cease breastfeeding.

     11. Male subjects should agree to adopt effective contraceptive measures from the first administration until 120 days after the final administration.

     Exclusion Criteria:

• 1. Presence of active metastases to the central nervous system or meningitis carcinomatosa.

  2. There is an uncontrolled abdominal infection, intestinal obstruction, grade 3 abdominal effusion, or risk of gastrointestinal fistula and perforation.

  3. Study participants received systemic immunosuppressant therapy within 28 days prior to treatment.

  4. Known to be allergic to any investigational product or any excipient of the investigational product.

  5. Diagnosed with other malignancies within the past 5 years, and the tumor is currently in a progressive stage or requires therapy (excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical carcinoma in situ that has undergone potential radical treatment).

  6. There is active autoimmune disease, and systemic therapy (including the use of disease-modifying drugs, corticosteroids, or immunosuppressants) has been received in the past two years. Replacement therapy (e.g., thyroxine replacement for hypothyroidism, insulin therapy for diabetes, or physiological glucocorticoid supplementation for adrenal/pituitary insufficiency) is not considered systemic therapy.

  7. Previously suffered from (non-infectious) pneumonia requiring glucocorticoid therapy, or currently suffering from pneumonia.

  8. There is an active infection requiring systemic therapy. 9. The presence of any history of disease, therapy, or laboratory abnormalities that could potentially interfere with the test results, affect the subject's full participation, or be deemed unsuitable for the subject's participation in the study by the Sub investigator.

  10. Past or current presence of mental disease or drug abuse, deemed by the sub investigator as unable to comply with trial requirements.

  11. Already pregnant or in lactation, or plans to become pregnant or cause pregnancy during the trial period (from the start of pre-screening or screening visit to 120 days after the final administration).

  12. Known infection with Human Immunodeficiency Virus (HIV1/2 antibody positive).

  13. Known to have hepatitis B (e.g., HBV Hepatitis B Surface Antigen positive) or hepatitis C (e.g., HCV RNA test positive).

  14. Received any live vaccine within 30 days prior to the first use of the investigational medicinal product.